Adhesions form as a natural part of the body's healing process after surgery or trauma in a process similar to the way that a scar forms. The term “adhesion” is typically used when the scar extends from one tissue to another, linking the two. In response to injury and bleeding the body deposits fibrin onto injured tissues. The fibrin acts like a glue to seal the injury and is the initial glue that builds the fledgling adhesion, generally referred at this point to be “fibrinous.” In body cavities such as the peritoneal, pericardial and synovial cavities, a family of fibrinolytic enzymes may act to limit the extent of the fibrinous adhesion, and may even dissolve it. In many cases however, the production or activity of these enzymes are compromised because of injury, and the fibrinous adhesion persists. If this is allowed to happen, tissue repair cells such as macrophages, fibroblasts and blood vessel cells, penetrate into the fibrinous adhesion, and unguided by a proper matrix lay down collagen and other matrix substances to form a permanent fibrous adhesion.
While some adhesions do not cause problems, others can prevent tissues and organs from moving freely, sometimes causing organs to become twisted or pulled from their normal positions. The sequence of adhesion formation is believed to occur and has been reported as follows: tissue ischemia, inflammation, fibrin deposition, fibrin organization, collagen formation, and maturation with the formation of adhesions. Surgeons use several agents to reduce adhesion formation at each of these steps. Physical barriers, including both mechanical and viscous solutions, are widely used to prevent adhesion formation by limiting and guiding tissue apposition during the critical stages of mesothelial repair. However, at least 50% of patients still develop significant adhesions. Moreover, there is no satisfactory way to monitor non-invasively the formation of unwanted adhesions after application of these techniques to a patient. Thus, improvements and further developments are critically needed.
Purified collagen from animals or humans is widely used in various medical devices, in research, and in cosmetics. However, the materials prepared from soluble purified collagen lack the macrostructure and organization seen in tissues. For example, the collagen fibers in tendon are highly aligned for maximal tensile strength, but also have a kinked structure to allow some give to the tissue. In contrast, the collagen in the cornea is arranged as small parallel transparent fibers. The collagen in the skin is arranged in bundles, not parallel, which allows more expansion and flexibility than seen with tendon. Each structure has obvious advantages to the tissue it comprises. Each structure is unique.
Collagen prepared from both human and animal sources has been shown to be safe and of minimal immunogenicity when implanted into humans. Collagen has the advantages that it is biocompatible, can form structures with high tensile strength, that the tensile strength of the constructs can be increased by covalent cross-linking and that the construct is replaced by normal tissue by repair and regeneration.
Methods to deposit collagen molecules in defined structures including aligned, woven and transparent materials convertible into bandages, sutures and multilayered structures for diverse indications are described in U.S. patent application Ser. Nos. 11/951,324, 11/986,263, 12/106,214, and 12/539,563, all of which are incorporated by reference herein in their entirety. One advantage of these collagen materials is that they closely approximate the natural structures of tissues, are biocompatible and induce the guided growth of cells attaching to them. The collagen materials appear to be an excellent substrate for applying mesenchymal and other stem cells to precise tissue sites. While these advances have been made, there is significant need for continued advancement and development of devices, constructs, implants and methods that promote and/or enhance tissue repair and regeneration, particularly constructs that provide an anti-adhesion barrier.